Human infection by Mycobacterium tuberculosis is endemic, with approximately 2 billion infected people worldwide. Because of the slow doubling time of M. tuberculosis and the risk of infection to researchers, other mycobacterial species like Mycobacterium marinum have been employed as a surrogate pathogen. M. marinum has a sequenced genome and is closely related to the M. tuberculosis complex. It has been shown to confer human TB-like chronic infection and pathology in some fish, such as the Japanese medaka (Oryzias latipes). Medaka also has a sequenced genome and has served as a laboratory fish model for toxicology, genotoxicity, etc. We have shown that the Medaka- M. marinum can model TB-like chronic infections and disease presentation. We have developed an approach of infection by utilizing larvae of Aedes aegypti (yellow fever mosquito) as vessels for the delivery of the bacteria to medaka. The passage of M. marinum through the caustic environment of the gastrointestinal tract of Mosquito larvae has been shown to increase the virulence of the bacteria when compared to using bacteria from culture. In addition, bacteria incubated in extracts of the macerated tissues of the mosquito larvae have also shown to activate bacteria comparable to the passage of M. marinum through the gastrointestinal tract of live mosquito larvae.
We have used Medaka-M. marinum model to study the fitness of mutants carrying defects in established virulence genes as well as novel mutant strains when compared to the wild-type reference strain when inoculated to the same animal. In this approach, the survival of the infected fish and colonization of the host organs were monitored as end points and bacteria were introduced through IP injections as well as an oral route of infection. Randomly isolated by Transposon mutagenesis, mimI mutant of M. marinum was previously shown in in vitro studies to be impaired in attachment and growth inside a macrophage was also shown to be severely defective in colonization in vivo when compared to the wild-type. Although the role played by mimI is not known, the in-silico and molecular characterization of its product is in progress.
|Advisor:||Ennis, Don G.|
|Commitee:||Chistoserdov, Andrei, Deaton, Lewis, Harrison, Lynn, Watson, Glen M.|
|School:||University of Louisiana at Lafayette|
|School Location:||United States -- Louisiana|
|Source:||DAI-B 76/08(E), Dissertation Abstracts International|
|Keywords:||Genotoxicology, Infection, Toxicology, Tuberculosis|
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